DALLAS – The addition of oral delayed-release dimethyl fumarate to conventional treatments for relapsing-remitting multiple sclerosis had safety and tolerability profiles similar to monotherapy with the drug, according to results from a phase II, open-label study.
In the EXPLORE study, the side effects most often recorded in 104 MS patients with breakthrough disease who were given oral delayed-release dimethyl fumarate (Tecfidera) combined with either interferon-beta or glatiramer acetate were mild to moderate flushing (42% and 53%, respectively), diarrhea (32% and 15%), and abdominal pain (21% and 6%). Previous phase III, placebo-controlled studies (DEFINE and CONFIRM) indicated similar adverse event rates for dimethyl fumarate (DMF) as monotherapy.
Whitney McKnight/Frontline Medical News
Dr. Jonathan Calkwood
"Adding Tecfidera to interferon-beta and glatiramer did not significantly increase the side effects of each of those drugs alone," Dr. Jonathan Calkwood said in an interview during a poster session at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
"White blood cell count declined, generally starting at about 2 months," said Dr. Calkwood, executive director of the Schapiro Center for Multiple Sclerosis at the Minneapolis Clinic of Neurology in Golden Valley, Minn. "This mirrored what we saw in the phase III studies, where white blood cell count went down and kind of stayed down."
The lymphocyte count decreased from baseline to week 24 by 22% in the delayed-release DMF plus interferon-beta group, and by 7% in the delayed-release DMF plus glatiramer acetate group. "This was also consistent with the phase III trials, where it goes down and stays down, but not enough to discontinue the medication," he said.
No malignancies were observed, and there were no deaths. There was a transient increase in liver transaminases, primarily in the interferon group, but according to Dr. Calkwood, this did not meet Hy’s law criteria. With the exception of one Clostridium difficile infection, there "was no real signal on infectious disease," he said.
For the study, the investigators enrolled patients aged 18-55 years who met McDonald disease criteria and who had an Expanded Disease Status Scale score of less than 5. At the time of enrollment, patients had been taking the same dose of interferon-beta or glatiramer acetate for at least 12 months and had at least one relapse within the past 12 months or a gadolinium-enhancing lesion within 6 weeks. Patients continued on their prescribed MS therapy for the first 2 months of the study before starting oral delayed-release DMF 240 mg three times daily in addition to their prescribed MS therapy for 6 months.
"The study was not really long enough to show differences in efficacy, although MRIs were done monthly as a safety measure," Dr. Calkwood said. However, if the question had been that oral delayed-release DMF would somehow interfere with rather than enhance the platform therapies’ respective ability to protect against breakthrough disease, he said that the imaging performed during the add-on therapy phase of the study showed fewer active lesions than the wash-in monotherapy phase. "It further supported what we thought we already knew."
Dr. Calkwood disclosed that he has financial relationships with Biogen Idec, maker of Tecfidera, as well as Teva Neuroscience, Bayer HealthCare, and EMD Serono. Biogen Idec sponsored this study.
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